Customized Targeted Therapy in Hodgkin Lymphoma

Diefenbach, Catherine; Advani, Ranjana H.

doi:10.1016/j.hoc.2013.10.004

Cited by 6 publications

(7 citation statements)

References 88 publications

(80 reference statements)

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“…Novel therapeutic approaches include the use of monoclonal antibodies, signal transduction inhibitors, immunotherapy, epigenetic agents such as histone deacetylase (HDAC) inhibitors and demethylating agents, and agents that target the tumor microenvironment [120]. Unfortunately, randomized clinical trials of these approaches have not yet been conducted in pediatric patients.…”

Section: Treatmentmentioning

confidence: 99%

Pediatric Hodgkin lymphoma- biomarkers, drugs, and clinical trials for translational science and medicine

et al. 2016

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Hodgkin lymphoma (HL) is a lymphoid malignancy that is typically derived from germinal-center B cells. EBV infection, mutations in NF-κB pathway genes, and genetic susceptibility are known risk factors for developing HL. CD30 and NF-κB have been identified as potential biomarkers in pediatric HL patients, and these molecules may represent therapeutic targets. Although current risk adapted and response based treatment approaches yield overall survival rates of >95%, treatment of relapse or refractory patients remains challenging. Targeted HL therapy with the antibody-drug conjugate Brentuximab vedotin (Bv) has proven to be superior to conventional salvage chemotherapy and clinical trials are being conducted to incorporate Bv into frontline therapy that substitutes Bv for alkylating agents to minimize secondary malignancies. The appearance of secondary malignancies has been a concern in pediatric HL, as these patients are at highest risk among all childhood cancer survivors. The risk of developing secondary leukemia following childhood HL treatment is 10.4 to 174.8 times greater than the risk in the general pediatric population and the prognosis is significantly poorer than the other hematological malignancies with a mortality rate of nearly 100%. Therefore, identifying clinically valuable biomarkers is of utmost importance to stratify and select patients who may or may not need intensive regimens to maintain optimal balance between maximal survival rates and averting late effects. Here we discuss epidemiology, risk factors, staging, molecular and genetic prognostic biomarkers, treatment for low and high-risk patients, and the late occurrence of secondary malignancies in pediatric HL.

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Section: Treatmentmentioning

confidence: 99%

Pediatric Hodgkin lymphoma- biomarkers, drugs, and clinical trials for translational science and medicine

et al. 2016

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“…Cure rates in classic Hodgkin lymphoma (cHL) range from 70 to 90 %, but complete recovery of patients is burdened by long-term toxicities of chemoradiation treatment, particularly heart and lung injury and secondary neoplasms [ 1 ]. Although in recent years interim [ 18 F]-fluoro-2-deoxy- d -glucose positron emission tomography carried out after 2 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) treatment (iPET-2) has emerged as a powerful predictor of treatment outcome in advanced-stage cHL patients [ 2 ], no other biomarkers have been shown capable of predicting treatment outcome at baseline with the same accuracy.…”

Section: Introductionmentioning

confidence: 99%

The favorable role of homozygosity for killer immunoglobulin-like receptor (KIR) A haplotype in patients with advanced-stage classic Hodgkin lymphoma

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Greco

Littera³

et al. 2016

J Hematol Oncol

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BackgroundInterim positron emission tomography after 2 cycles of ABVD (iPET-2) is a good predictor of outcome in advanced-stage classic Hodgkin lymphoma. So far, there are no other prognostic biomarkers capable of identifying chemotherapy refractory patients with comparable accuracy. Despite the considerable amount of evidence suggesting that antitumor immune surveillance is downregulated in classic Hodgkin lymphoma (cHL), few data exist on the impairment of natural killer cell function and the role of their killer immunoglobulin-like receptors (KIRs).MethodsWe investigated KIR gene frequencies, KIR haplotypes, and KIR-ligand combinations in a cohort of 135 patients with advanced-stage classic Hodgkin lymphoma and 221 healthy controls. We furthermore evaluated the correlation of KIR genes and KIR haplotypes with the achievement of negative iPET-2.ResultsIn the cohort of patients, the 5-year overall survival and progression-free survival were 93.6 and 79 %, respectively. Homozygosity for KIR A haplotype and the HLA-C1 KIR ligand (KIR-AA/C1C1) was significantly higher in healthy controls (15.7 vs. 4.8 %, p = 0.001). The KIR-AA genotype resulted to have a significant predictive power for achieving iPET-2 negativity (p = 0.039).ConclusionsHomozygosity for KIR A haplotype offers protection against classic Hodgkin lymphoma. The association found for the KIR-AA genotype and achievement of negative iPET-2 suggests that KIR-AA could be used in clinical practice to enhance the chemosensitivity predictive power of iPET-2. Our results point to the possibility of adapting treatment strategies based on the combination of KIR biomarkers and PET scan.

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“…In 2013, ~9,000 cases of HL were diagnosed in the United States and 1,180 individuals were predicted to succumb to the disease (8). Nodular sclerosing HL is more common in the developed countries of Europe and America, while mixed cellularity HL is more common in China.…”

Section: Discussionmentioning

confidence: 99%

“…Nodular sclerosing HL is more common in the developed countries of Europe and America, while mixed cellularity HL is more common in China. Classic HL represents ~10% of all lymphomas diagnosed annually in the developing world (8). MM is a clonal B-cell disorder with characteristic B-lymphocyte and plasma cell proliferation and accumulation.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, the OS and progression-free survival of MM has been increasing due to the application of targeted drugs, including bortezomib, thalidomide and lenalidomide (7). The coexistence of HL and MM is rare (8)(9)(10). The current study reports the case of a patient who presented with HL and MM at the same time, for which a good outcome was achieved using chemotherapy.…”

Section: Introductionmentioning

confidence: 90%

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Simultaneous occurrence of Hodgkin's lymphoma and multiple myeloma: A case report and review of the literature

et al. 2016

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Abstract. Hodgkin's lymphoma (HL) is a type of hematological neoplasm that generally appears alone, with a low incidence. The majority of cases histopathologically present as B-cell lymphoma. Multiple myeloma (MM) is defined as the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin (Ig). The coexistence of HL and MM is rare, however, the present study reports such a case. On May 31, 2012, a 45-year-old man was diagnosed with HL, stage III, 31 months ago. At the same time, computed tomography and magnetic resonance imaging showed osteolytic lesions, a significant increase in IgA λ chains, and multiple myeloma cells on bone marrow aspiration. Following 8 cycles of chemotherapy, the patient received maintenance treatment with thalidomide and dexamethasone. During 2 years of follow-up, the patient has maintained a complete response for HL and a stable disease state for MM. The coexistence of HL and MM is rare.Further study of such cases may explain the associations between these two tumors and aid the production of effective treatment options.

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Customized Targeted Therapy in Hodgkin Lymphoma

Cited by 6 publications

References 88 publications

Pediatric Hodgkin lymphoma- biomarkers, drugs, and clinical trials for translational science and medicine

Pediatric Hodgkin lymphoma- biomarkers, drugs, and clinical trials for translational science and medicine

The favorable role of homozygosity for killer immunoglobulin-like receptor (KIR) A haplotype in patients with advanced-stage classic Hodgkin lymphoma

Simultaneous occurrence of Hodgkin's lymphoma and multiple myeloma: A case report and review of the literature

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